The goal of this subproject is to investigate pharyngoesophageal and laryngeal function in health and in conditions which lead to gastroesophageal-pharyngeal reflux and laryngeal aspiration. Two specific objectives are listed: 1) to determine the pathophysiological basis of laryngeal complications of reflux and 2) to investigate the afferent sensory pathways in animals and humans which influence the occurrence and frequency of gastroesophago-pharyngeal reflux. These objectives will be met by performing 15 studies. These can be grouped into human and animal studies, and further subdivided as follows: Human studies of gastroesophageal-pharyngeal reflux and its consequences. These include: Characterization and quantification of gastroesophago-pharyngeal reflux, mechanisms of gastroesophago-pharyngeal reflux, studies of esophago-glottal closure reflux, stimulation of esophago-glottal reflex in response to gastroesophageal reflux. These studies will be performed in four groups of subject/patients: controls (male and female), patients with esophageal reflux but no laryngeal symptoms, patients with acid damage to the larynx (acid laryngitis), and patients with laryngeal symptoms but no endoscopic evidence of acid laryngitis. The results from each group will be compared. The presence of acid will be detected by intraluminal pH probes, sphincter function by specialized Dent sleeves, common cavity events and peristalsis by intraluminal pressure detectors, and glottal closure by nasal videoendoscopy. Human studies of other esophageal and pharyngeal reflexes include: studies of secondary peristalsis, pharyngo-UES contractile reflex and reflexive pharyngeal swallow, pharyngoglottal adduction reflex, inhibitory effect of pharyngeal water stimulation on esophageal peristalsis and bolus transport, and inhibitory effect of pharyngeal stimulation on LES tone and gastroesophageal reflux. These studies will utilize the same techniques and study the same control/patient groups as in the studies outlined above. In addition, secondary peristalsis will be stimulated by a barostat connected to a long thin non-compliant balloon. Videofluorography will also be used to document bolus transport. The last set of human studies examines esophageal sensation. In the same four groups of controls/patients, cerebral activation of the cortex by esophageal stimulation will be studied by fMRI. After stimulation with intraesophageal balloons, hot and cold water and acid, changes in cerebral blood flow will be documented by fMRI. Animal studies of pharyngeal and esophageal reflexes include: studies of the pharyngoesophageal inhibitory reflexes, studies of the pharyngoglottal closure reflex, determination of stimuli for pharyngo-UES, pharyngo-glottal, contractile reflexes, esophago-glottal and esophageal-UES contractile. These studies will be done in decerebrate cats. Laryngeal muscle function will be measured by electromyography or by direct observation. Nerves will be stimulated or transected to study pathways and mucosal anesthetic or capsaicin will disable mucosal receptors. In some studies, anesthetized opossums will be used so that inhibition of nitric oxide can be done by intra-arterial infusions of nitric oxide inhibitors. Isolated vagal fiber single unit electrode recordings will be made.